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인간 기관지 평활근 세포에서 Dexamethasone의 PDGF와 TGF-β에 의해 증강된 Vascular Endothelial Growth Factor 생성 억제 효과

Dexamethasone Attenuates PDGF- and TGF-β-enhanced Vascular Endothelial Growth Factor Production in Cultured Human Bronchial Smooth Muscle Cells

김덕수|박문수|정혜림|심재원|심정연|유명환|서보실
대한 소아알레르기 호흡기학회 (The Korean Academy Of Pediatric Allergy And Respiratory Disease)|2006.06|Allergy Asthma & Respiratory Disease (알레르기 천식 호흡기질환)|제16권 제2호|pp. 142-149

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주제분류소아과학

초록

목 적 : 인간 기관지 평활근 세포는 천식에서 기관지 운동의 톤을 조절할 뿐만 아니라 기도의 면역조절과 기도개형에서 중요한 역할을 담당하고 있다. VEGF는 다양한 기능을 가지고 있는 사이토카인으로 천식양 표현형을 유도하며 염증, 부종, 혈관 개형, 점액질 화생(mucus metaplasia), 상피세포하 섬유화, 기도 항원 감작 그리고 항원유도 Th2 염증 반응을 일으킨다. 또한 TGF-β는 기도개형에서 인간 기관지 평활근세포의 성장을 조절하는 중요한 사이토카인으로 알려져 있으나 천식 기도개형에서의 역할은 명확하지 않다. 본 연구에서는 배양된 기관지 평활근 세포에서 dexamethasone이 PDGF와 TGF-β의 자극에 의한 VEGF의 분비에 어떠한 영향을 미치는지 알아보고자 하였다.방 법 : 10% FCS-DMEM 배지에서 배양된 사람 기관지 평활근세포를 48시간 동안 무혈청 배지에서 성장을 정지시킨 후 dexamethasone (10-5, 10-6 M)와 TGF-β(10 ng/mL)로 전처치하였다. 16시간 후 PDGF(20 ng/mL)로 자극하여 24시간 뒤 배양 상층액을 추출 후 VEGF의 ELISA 측정 전까지 영하 80도에 보관하였다.

Abstract

Purpose : Human bronchial smooth muscle cell(HBSMC) plays an important role in the remodeling of the airways in asthma. Vascular endothelial growth factor(VEGF) is a multifunctional cytokine, which induces edema, angiogenesis, vascular remodeling, mucus metaplasia, subepithelial fibrosis, and antigen-induced Th2 inflammation. Transforming growth factor-beta(TGF-β) is a growth modulator of HBSMC and an important cytokine in airway remodeling. We investigated the effect of dexamethasone on the release of VEGF from HBSMC stimulated with platelet-derived growth factor(PDGF) and TGF-β. Methods : HBSMC cultured in 10 percent FCS-DMEM media was growth-arrested in serum-deprived medium for 48 hours. Dexamethasone and TGF-β were added and incubated for 16 hours before stimulation with PDGF. After 24 hours of stimulation, culture medium was harvested and stored at -80℃ until ELISA for VEGF was performed. Results : The release of VEGF was significantly increased after stimulation with PDGF (P<0.01). The production of VEGF pretreated with TGF-β before stimulation with PDGF was higher than those without TGF-β pretreatment(P<0.01). Dexamethasone suppressed the release of VEGF in HBSMC stimulated with PDGF(P<0.01), TGF-β and PDGF(P<0.01). Conclusion : PDGF and TGF-β may be one of the key mediators in inducing airway remodeling and glucocorticoid, and can be used as useful therapies to prevent airway vascular remodeling by modulating the VEGF on airway smooth muscle cells.

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